Neurons in lamina I were antidromically identified as having axons projecting to the brain (lamina I projection neurons) and then physiologically characterized with respect to their cutaneous sensitivity. Nearly all of the neurons were found to respond exclusively to noxious stimuli. Some of the neurons were determined to project to the parabrachial area, an area in the brain stem that has not been previously considered as a target on nociceptive inputs. Intracellular staining showed that lamina I projection neurons belong to diverse morphological types. Immunocytochemical techniques showed that lamina I projection neurons in general, as well as those that project to the parabrachial area, are invariably contacted by serotonergic axons that descend from the raphe nuclei. A systematic search of the dorsal horn revealed several morphologically distinct populations of neurons that might mediate the ability of input from low-threshold mechanoreceptors to inhibit pain. In particular, a population of small interneurons in lamina III was identified and found to have the electrophysiological and anatomical characteristics appropriate for interneurons producing the inhibitory postsynaptic potentials seen in projection neurons after the activation of low-threshold mechanoreceptors.